High-throughput identification of tuna (Thunnus spp.) larvae in the Gulf of Mexico using unlabelled-probe high-resolution melting analysis.

The genus Thunnus (family Scombridae) comprises eight species of tunas of which all but one are targeted by industrialized fisheries. Although intact individuals of these species can be distinguished by morphological characteristics, researchers and managers often rely on dressed, frozen, juvenile or larval fish samples, which often necessitates the identification of molecular species. Here the authors investigate short amplicon (SA) and unlabelled probe high-resolution melting analysis (UP-HRMA) as a low-cost, high-throughput molecular genotyping assay capable of distinguishing between albacore tuna (Thunnus alalunga), blackfin tuna (Thunnus atlanticus), bigeye tuna (Thunnus obesus), Atlantic bluefin tuna (Thunnus thynnus) and yellowfin tuna (Thunnus albacares) in the Gulf of Mexico. Although SA-HRMA of variable regions in the NADH dehydrogenase subunit 4 (ND4) and subunit 5 (ND5), and subunit 6 (ND6) of the mtDNA genome did yield some species-specific diagnostic melting curves (e.g., ND4 assay can reliably distinguish Atlantic bluefin tuna), genotype masking produced excessive variation in melting curves for reliable multi-species identification. To minimize the genotyping masking of SA-HRMA a 26 base pair long UP containing four SNPs was developed within a 133 bp segment of ND4. The UP-HRMA is able to reliably distinguish Gulf of Mexico species T. thynnus, T. obesus, T. albacares and T. atlanticus by UP melting temperature at 67, 62, 59 and 57°C, respectively. The developed UP-HRMA assay is a lower-cost, higher-throughput, alternative to previously published molecular assays for tuna identification that can be easily automated for large data sets, including ichthyological larval surveys, fisheries specimens lacking distinguishing morphological characteristics or detection of fraudulent trading of tuna species.

Design and discovery of C2-fluoroalkyl iminothiazine dioxides as BACE inhibitors.

This paper describes the structure-activity-relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta secretase inhibitors. Key discoveries include reduced amidine basicity and its effect on Pgp, cell potency, and efficacy in various preclinical in vivo efficacy animal models. Findings from these structure-activity-relationships are discussed.

High-speed hyperspectral four-wave-mixing microscopy with frequency combs.

A four-wave-mixing, frequency-comb-based, hyperspectral imaging technique that is spectrally precise and potentially rapid, and can in principle be applied to any material, is demonstrated in a near-diffraction-limited microscopy application.

A comparative network analysis of eating disorder psychopathology and co-occurring depression and anxiety symptoms before and after treatment.

BACKGROUND: Network analysis is an emerging approach in the study of psychopathology, yet few applications have been seen in eating disorders (EDs). Furthermore, little research exists regarding changes in network strength after interventions. Therefore the present study examined the network structures of ED and co-occurring depression and anxiety symptoms before and after treatment for EDs. METHOD: Participants from residential or partial hospital ED treatment programs (N = 446) completed assessments upon admission and discharge. Networks were estimated using regularized Graphical Gaussian Models using 38 items from the Eating Disorders Examination-Questionnaire, Quick Inventory of Depressive Symptomatology, and State-Trait Anxiety Inventory. RESULTS: ED symptoms with high centrality indices included a desire to lose weight, guilt about eating, shape overvaluation, and wanting an empty stomach, while restlessness, self-esteem, lack of energy, and feeling overwhelmed bridged ED to depression and anxiety symptoms. Comparisons between admission and discharge networks indicated the global network strength did not change significantly, though symptom severity decreased. Participants with denser networks at admission evidenced less change in ED symptomatology during treatment. CONCLUSIONS: Findings suggest that symptoms related to shape and weight concerns and guilt are central ED symptoms, while physical symptoms, self-esteem, and feeling overwhelmed are links that may underlie comorbidities in EDs. Results provided some support for the validity of network approaches, in that admission networks conveyed prognostic information. However, the lack of correspondence between symptom reduction and change in network strength indicates that future research is needed to examine network dynamics in the context of intervention and relapse prevention.

Optimum repetition rates for dual-comb spectroscopy.

The determination of the properties (i.e. line center, width, and amplitude) of a spectral line is simulated using a Monte Carlo method. For dual-comb spectroscopy, ideal repetition rates emerge for both the signal and LO combs that do not correspond to the repetition rates that possess the highest signal-to-noise ratio. The determination is even more accurate when the repetition rates have an arbitrary near-harmonic ratio. The simulation results are generalized to allow for the comparison of any two spectroscopic systems (i.e. not just comb-based systems) by performing the simulations as a function of the spectral point spacing and signal-to-noise ratio of the acquired data.

Identifying a male clinical cutoff on the Eating Disorder Examination-Questionnaire (EDE-Q).

OBJECTIVE: Evidence suggests that eating disorders (EDs) may be under-detected in males. Commonly used measures of EDs such as the Eating Disorder Examination-Questionnaire (EDE-Q) were initially developed within female samples, raising concern regarding the extent to which these instruments may be appropriate for detecting EDs in males. The current study used receiver operating characteristic curve analysis to (a) examine the accuracy of the EDE-Q global score in correctly classifying males with and without clinically significant ED pathology, and (b) establish the optimal EDE-Q global clinical cutoff for males. METHOD: Participants were a clinical sample of 245 male ED patients and a control sample of 205 male undergraduates. RESULTS: Eating Disorder Examination-Questionnaire global scores demonstrated moderate-high accuracy in predicting ED status (area under the curve = 0.85, 95% CI: 0.82-0.89). The optimal cutoff of 1.68 yielded a sensitivity of 0.77 and specificity of 0.77. DISCUSSION: Overall, results provide preliminary support for the discriminant validity of EDE-Q scores among males. However, concerns remain regarding the measure's ability to comprehensively assess domains of disordered eating most relevant to males. Therefore, careful attention to the possibility for measurement bias and continued evaluation of the scale in males is encouraged.

Affective predictors of the severity and change in eating psychopathology in residential eating disorder treatment: The role of social anxiety.

Despite evidence documenting relationships between eating disorder (ED) psychopathology, depression, and anxiety, little is known regarding how social anxiety is related to ED symptoms in treatment. Therefore this study examined associations between depression, general anxiety, social anxiety, and ED psychopathology at the beginning and end of treatment (EOT) among patients (N = 380) treated in a residential ED program. Participants completed measures of ED psychopathology and affective variables. Higher depression and general anxiety, but not social anxiety, were related to higher ED psychopathology at baseline. However, social anxiety emerged as a unique predictor of ED psychopathology at EOT such that participants with higher social anxiety evidenced less improvement in ED psychopathology. Findings suggest that social anxiety has specific relevance to treatment in EDs, which may reflect shared mechanisms and underlying deficits in emotion regulation.

Male clinical norms and sex differences on the Eating Disorder Inventory (EDI) and Eating Disorder Examination Questionnaire (EDE-Q).

OBJECTIVE: Evidence indicates that males account for a significant minority of patients with eating disorders (EDs). However, prior research has been limited by inclusion of small and predominantly non-clinical samples of males. This study aimed to (1) provide male clinical norms for widely used ED measures (Eating Disorder Examination Questionnaire [EDE-Q] and Eating Disorder Inventory-3 [EDI-3]) and (2) examine sex differences in overall ED psychopathology. METHOD: Participants were 386 male and 1,487 female patients with an ED diagnosis aged 16 years and older who completed the EDE-Q and EDI-3 upon admission to a residential or partial hospital ED treatment program. RESULTS: Normative data were calculated for the EDE-Q (global and subscales) and the EDI-3 (drive for thinness, body dissatisfaction, and bulimia). Analyses of variance (ANOVAs) used to examine sex, ED diagnosis, and their interaction in relation to overall ED psychopathology revealed a consistent pattern of greater severity among females for ED psychopathology. DISCUSSION: This study provides clinical norms on the EDE-Q and the EDI-3 for males with clinically diagnosed EDs. It is unclear whether the greater severity observed in females reflects qualitative differences in ED presentation or true quantitative differences in ED severity. Additional research examining the underlying nature of these differences and utilizing male-specific ED measures with clinical samples is warranted.

CNS amyloid-ß, soluble APP-α and -ß kinetics during BACE inhibition.

BACE, a ß-secretase, is an attractive potential disease-modifying therapeutic strategy for Alzheimer's disease (AD) as it results directly in the decrease of amyloid precursor protein (APP) processing through the ß-secretase pathway and a lowering of CNS amyloid-ß (Aß) levels. The interaction of the ß-secretase and α-secretase pathway-mediated processing of APP in the rhesus monkey (nonhuman primate; NHP) CNS is not understood. We hypothesized that CNS inhibition of BACE would result in decreased newly generated Aß and soluble APPß (sAPPß), with increased newly generated sAPPα. A stable isotope labeling kinetics experiment in NHPs was performed with a (13)C6-leucine infusion protocol to evaluate effects of BACE inhibition on CNS APP processing by measuring the kinetics of sAPPα, sAPPß, and Aß in CSF. Each NHP received a low, medium, or high dose of MBI-5 (BACE inhibitor) or vehicle in a four-way crossover design. CSF sAPPα, sAPPß, and Aß were measured by ELISA and newly incorporated label following immunoprecipitation and liquid chromatography-mass spectrometry. Concentrations, kinetics, and amount of newly generated APP fragments were calculated. sAPPß and sAPPα kinetics were similar, but both significantly slower than Aß. BACE inhibition resulted in decreased labeled sAPPß and Aß in CSF, without observable changes in labeled CSF sAPPα. ELISA concentrations of sAPPß and Aß both decreased and sAPPα increased. sAPPα increased by ELISA, with no difference by labeled sAPPα kinetics indicating increases in product may be due to APP shunting from the ß-secretase to the α-secretase pathway. These results provide a quantitative understanding of pharmacodynamic effects of BACE inhibition on NHP CNS, which can inform about target development.

Short-form mindfulness-based stress reduction reduces anxiety and improves health-related quality of life in an inner-city population.

Mindfulness-based stress reduction is a mindfulness-based intervention that is an effective treatment modality for many conditions including stress, anxiety, and depression. Using data from 23 patients who completed a short-form mindfulness-based stress reduction course at a federally qualified health center, a quasi-experimental design was used to assess the impact of participation on self-reported anxiety, stress, mindfulness, and quality of life. Mindfulness and stress showed improvements from pre- to posttests, but neither difference achieved statistical significance. Participants showed statistically significant decreases in anxiety (7-item Generalized Anxiety Disorder scale score: 7.8-4.4; P = .005) and improvements in health-related quality of life including the 36-item Medical Outcomes Study Short Form Health Survey Mental Component Summary (+9.1; P = .001), Physical Functioning (+6.6; P = .039), Vitality (+16.1; P = .001), Social Functioning (+16.9; P = .003), Role Physical (+16.8; P = .016), and Mental Health (+15.6; P < .001) subscales. These findings suggest that an abbreviated mindfulness-based stress reduction course can serve to reduce anxiety and improve quality of life in an underserved population.

The quality of mental health care for veterans of Operation Enduring Freedom/Operation Iraqi Freedom.

BACKGROUND: Some Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans experience serious mental health (MH) problems. As OEF/OIF soldiers leave active military duty, their growing numbers pose a challenge to the Department of Veterans Affairs (VA) in delivering high-quality mental health/substance-use disorder (MH/SUD) care. OBJECTIVE: To determine whether the quality of MH/SUD care provided by the VA differs by OEF/OIF veteran status. METHODS: Veterans with selected MH/SUDs were identified from administrative records using diagnostic codes. OEF/OIF service was determined based on Defense Manpower Data Center separation files. Eleven processes of care and 7 utilization performance indicators were examined. Regression analyses were adjusted for veteran demographic and clinical characteristics to test for differences in care by OEF/OIF status. RESULTS: Of the 836,699 veterans with selected diagnoses who received MH/SUD treatment in FY2007, 52,870 (6.3%) were OEF/OIF veterans. In unadjusted analyses, OEF/OIF veterans were more likely to receive evidence-based care processes captured by 6 of the 11 dichotomous performance indicators examined; however, among those receiving psychotherapy encounters, OEF/OIF veterans received significantly fewer visits (6.9 vs. 9.7, P<0.0001). In adjusted analyses, only postdischarge follow-up remained meaningfully higher for OEF/OIF veterans. CONCLUSIONS: Efforts to maintain and/or increase OEF/OIF veteran participation in VA MH/SUD services should be informed by their characteristics, such as younger age and better physical health relative to other veterans.

Addressing the fouling of in situ ultraviolet-visual spectrometers used to continuously monitor water quality in brackish tidal marsh waters.

The introduction of portable in situ ultraviolet-visual spectrometers has made possible the collection of water quality parameters at a high frequency in dynamic systems such as tidal marshes. The usefulness of this technology is inhibited by fouling of the instrument's optics. In this study, a spectrometer fitted with manufacturer-recommended compressed air optical cleaning was installed in a brackish marsh to determine if fouling interfered with measurements between bi-weekly servicing. During a 2-wk period, the absorbance measured in air at 220 nm increased from 9 to 549 m, indicating major fouling. An antifouling system was developed that reduced the time of exposure of the optics to stream water and used a pressurized fresh water cleaning. After implementation of the system, the absorbance in air increased to at most 63 m after 2 wk of data collection. The dramatic reduction in fouling will allow quality long-term data to be collected using this technology.

Do men and women differ in their perceptions of stalking: an exploratory study among college students.

Stalking is a crime that can terrify its victims and ultimately take a severe emotional toll. Although a growing body of research has examined stalking experiences and reactions of victims, there has been far less research on whether men and women differ in their perceptions of stalking. Toward this end, a survey of college students at a large public 4-year Midwestern university was undertaken. We examined differences is how men and women view stalking and whether gender differences were moderated by prior stalking experience. Specifically, we examined whether there were gender differences in perceptions of the pervasiveness of stalking, the harm stalking does, who tends to be stalked, if stalking mainly involves former relational partners, possible motivations for stalking, the line between courtship and stalking, and notions of victim blaming. We found significant differences in stalking views between men and women on all the measures, except for perceptions of the line between courtship and stalking. Women tended to perceive stalking as more pervasive and harmful. Men were more likely to perceive stalking as involving strangers and to blame the victim for the stalking. Female and male respondents also differed in their perceptions of motivations for stalking. Prior victim stalking experience did not moderate the gender differences. Although being a prior stalking victim had a significant association with 4 of the 7 stalking perception variables, its effect sizes were smaller than that of gender.

Development of Gelled-Oil Nanoparticles for the Encapsulation and Release of Berberine.

In this study, a new drug carrier based on gelled-oil nanoparticles (GNPs) was designed and synthesized for the encapsulation and release of the model hydrophobic drug, berberine chloride (BCl). Two compositions with different oil phases were examined, sesame oil (SO) and cinnamaldehyde (Cin), which were emulsified with water, stabilized with Tween 80 (Tw80), and gelled using an N-alkylated primary oxalamide low-molecular-weight gelator (LMWG) to give stable dispersions of GNPs between 100 and 200 nm in size. The GNP formulation with Cin was significantly favored over SO due to (1) lower gel melting temperatures, (2) higher gel mechanical strength, and (3) significantly higher solubility, encapsulation efficiency, and loading of BCl. Also, the solubility and loading of BCl in Cin were significantly increased (at least 7-fold) with the addition of cinnamic acid. In vitro release studies showed that the release of BCl from the GNPs was independent of gelator concentration and lower than that for BCl solution and the corresponding nanoemulsion (no LWMG). Also, cell internalization studies suggested that the N-alkylated primary oxalamide LMWG did not interfere with the internalization efficiency of BCl into mouse mast cells. Altogether, this work demonstrates the potential use of these new GNP formulations for biomedical studies involving the encapsulation of drugs and nutraceuticals and their controlled release.

Evaluating Ultrasonicator Performance for Cyanobacteria Management at Freshwater Sources.

Algal blooms consisting of potentially toxic cyanobacteria are a growing source water management challenge faced by water utilities globally. Commercially available sonication devices are designed to mitigate this challenge by targeting cyanobacteria-specific cellular features and aim to inhibit cyanobacterial growth within water bodies. There is limited available literature evaluating this technology; therefore, a sonication trial was conducted in a drinking water reservoir within regional Victoria, Australia across an 18-month period using one device. The trial reservoir, referred to as Reservoir C, is the final reservoir in a local network of reservoirs managed by a regional water utility. Sonicator efficacy was evaluated through qualitative and quantitative analysis of algal and cyanobacterial trends within Reservoir C and surrounding reservoirs using field data collected across three years preceding the trial and during the 18-month duration of the trial. Qualitative assessment revealed a slight increase in eukaryotic algal growth within Reservoir C following device installation, which is likely due to local environmental factors such as rainfall-driven nutrient influx. Post-sonication quantities of cyanobacteria remained relatively consistent, which may indicate that the device was able to counteract favorable phytoplankton growth conditions. Qualitative assessments also revealed minimal prevalence variations of the dominant cyanobacterial species within the reservoir following trial initiation. Since the dominant species were potential toxin producers, there is no strong evidence that sonication altered Reservoir C's water risk profiles during this trial. Statistical analysis of samples collected within the reservoir and from the intake pipe to the associated treatment plant supported qualitative observations and revealed a significant elevation in eukaryotic algal cell counts during bloom and non-bloom periods post-installation. Corresponding cyanobacteria biovolumes and cell counts revealed that no significant changes occurred, excluding a significant decrease in bloom season cell counts measured within the treatment plant intake pipe and a significant increase in non-bloom season biovolumes and cell counts as measured within the reservoir. One technical disruption occurred during the trial; however, this had no notable impacts on cyanobacterial prevalence. Acknowledging the limitations of the experimental conditions, data and observations from this trial indicate there is no strong evidence that sonication significantly reduced cyanobacteria occurrence within Reservoir C.

The Alzheimer's disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130.

BACKGROUND: The protease BACE1 is a major drug target for Alzheimer's disease, but chronic BACE1 inhibition is associated with non-progressive cognitive worsening that may be caused by modulation of unknown physiological BACE1 substrates. METHODS: To identify in vivo-relevant BACE1 substrates, we applied pharmacoproteomics to non-human-primate cerebrospinal fluid (CSF) after acute treatment with BACE inhibitors. RESULTS: Besides SEZ6, the strongest, dose-dependent reduction was observed for the pro-inflammatory cytokine receptor gp130/IL6ST, which we establish as an in vivo BACE1 substrate. Gp130 was also reduced in human CSF from a clinical trial with a BACE inhibitor and in plasma of BACE1-deficient mice. Mechanistically, we demonstrate that BACE1 directly cleaves gp130, thereby attenuating membrane-bound gp130 and increasing soluble gp130 abundance and controlling gp130 function in neuronal IL-6 signaling and neuronal survival upon growth-factor withdrawal. CONCLUSION: BACE1 is a new modulator of gp130 function. The BACE1-cleaved, soluble gp130 may serve as a pharmacodynamic BACE1 activity marker to reduce the occurrence of side effects of chronic BACE1 inhibition in humans.

Standardizing protected species observer requirements in the United States.

Currently, there is considerable geographic variation in the data-collection requirements and procedures for US-permitted seismic surveys conducted for energy and research purposes. The development of standards to train PSOs, standardization of data collection, submission standards, and development of quality assurance and quality control standards will make data analysis more efficient and robust. The implementation of national standards for the Seismic Survey PSO Programs will increase the integrity of data collected and reported for more effective protected species management.

Practical Strategies and Tools for Use by Occupational and Environmental Medicine Departments During COVID-19 Pandemic Surges.

OBJECTIVES: Occupational and environmental medicine (OEM) departments in healthcare institutions can be quickly overwhelmed when COVID-19 infection rates rapidly and simultaneously increase in the workforce and the patients served. Our goal is to present a detailed toolkit of practical approaches for use by front-line OEM specialists to address workforce management tasks during pandemic surges. METHODS: Specific focus is on tasks related to employee symptom triage, exposure risk assessment, workplace contact tracing, and work restrictions. RESULTS: Tools include strategies used by customer call centers, two decision support algorithms (exposure due to cohabitation or non-cohabitation), a color-coded employee case tracking tool, a contact tracing protocol, and documentation templates that serve as memory aids for encounters. CONCLUSIONS: These tools are created with commonly used software. Implementation is feasible in most front-line OEM settings, including those with limited resources.